Lentivirus介导神经营养因子-3促进脊髓损伤大鼠功能恢复  

Lentivirus-mediated neurotrophic factor-3 in the injured adult rat spinal cord improves hind limb functional recovery

作　　者：蔡培强[1] 汤逊[1] 林月秋[1] Oudega Mart 徐林[2] Blits B 阳运康[1] M.OUDEGA 

机构地区：[1]成都军区昆明总医院骨科 [2]中国科学院昆明动物研究所 [3]Graduate School for Neurosciences Amsterdam,Netherlands Institute for Brain Research,Amsterdam,The Netherlands [4]The Miami Project to Cure Paralysis,University of Miami School of Medicine,Miami,FL33101,USA

出　　处：《中华创伤杂志》2005年第7期485-490,共6页Chinese Journal of Trauma

基　　金：云南省自然科学基金资助项目(2002C0070M)

摘　　要：目的探讨Lentivirus介导分泌神经营养因子-3(NT-3)直接体内转基因治疗大鼠脊髓损伤作用和机制。方法将28只Wistar大鼠在T10水平制成半横断损伤模型,随机分为体内转基因治疗组和损伤对照组,每组14只;用携带NT-3和绿色荧光蛋白(GFP)的Lentivirus对大鼠行直接体内转基因治疗;荧光显微镜观察体内转基因表达,后肢运动功能评分法(BBB评分)检测大鼠后肢功能恢复情况。结果用荧光显微镜检测到损伤脊髓内有较多的持续表达转基因的细胞;BBB评分结果显示,从伤后第4周开始,实验组大鼠后肢功能较对照组明显恢复(P<0.01),至第10周时,实验组和对照组BBB分差增大,达3.3分。结论Lentivirus是一种有效的转基因载体,由Lentivirus介导分泌NT-3的直接体内转基因治疗能够明显促进损伤脊髓的功能恢复。Objective To explore the therapeutic mechanism and effect of Lentivirus-mediated neurotrophic factor-3 (NT-3) gene transfer in treatment of the injured adult rat spinal cord. Methods Hemisection of spinal cord at the level of T10 were produced in 28 adult Wistar rats that were randomly divided into two groups (n=14): transgenic therapy group and control group. The experimental group was treated directly in vivo with Lentivirus that contained NT-3 and green fluorescence protein (GFP). Then, the transgenic expression in vivo was detected with fluorescence microscope and the recovery of function estimated with the method of BBB. Results GFP showed many cells that had expressed objective gene for two months in vivo and BBB detected that the hind-limb function of the injured rat had acquired obvious improvement. Conclusions Lentivirus-mediated NT-3 gene transfer can promote the functional recovery of injured spinal cord by improving the local microenvironment of the injured spinal cord. Additionally, Lentivirus is an effective transgenic vector that can be applied widely in the basic study and the further clinical application for treatment of the spinal cord injury.

关 键 词：神经营养因子-3 功能恢复 脊髓损伤 介导 Wistar大鼠 转基因治疗 横断损伤模型 绿色荧光蛋白 后肢运动功能 NT-3 后肢功能 转基因表达 显微镜检测 转基因载体 对照组 损伤作用 微镜观察 恢复情况 损伤脊髓 BBB 实验组 体内 

分 类 号：R651.12[医药卫生—外科学]